Synthesizing pathogen- and infection-specific estimates of the burden of antimicrobial resistance in Europe for health-technology assessment: gaps, heterogeneity, and bias
Authors: Julie V. Robotham, Evelina Tacconelli, Venanzio Vella, Marlieke E.A. de Kraker
Journal: Clinical Microbiology and Infection (2023)

Antimicrobial resistance (AMR) causes a high burden of disease. The European Centre for Disease Prevention and Control has estimated that in 2019, AMR caused 865 767 infections, 38 710 attributable deaths, and 1 101 288 disability-adjusted life years, in Europe [ [1] European Centre for Disease Prevention and ControlAssessing the health burden of infections with antibiotic-resistant bacteria in the EU/EEA, 2016-2020. ECDC, Stockholm2022 Date accessed: July 9, 2023 https://www.ecdc.europa.eu/sites/default/files/documents/Health-burden-infections-antibiotic-resistant-bacteria.pdf Google Scholar ]. Because increasing rates of AMR further reduce the effectiveness of last resort antibiotics, novel treatment strategies are urgently needed. According to Butler and Paterson [ [2] Butler M.S. Paterson D.L. Antibiotics in the clinical pipeline in October 2019. J Antibiot (Tokyo). 2020; 73: 329-364https://doi.org/10.1038/s41429-020-0291-8 Crossref PubMed Scopus (172) Google Scholar ], between 2017 and 2021, 12 new antibiotics were approved, of which only vaborbactam belonged to a new class. Among 16 antimicrobial agents in phase III or under regulatory evaluation, only 4 have new modes of action. Vaccines and monoclonal antibodies (mAbs) could offer a promising alternative for prevention or treatment of infections [ [3] IA2030 immunization agenda 2030. World Health Organization, 2020https://www.who.int/teams/immunization-vaccines-and-biologicals/strategies/ia2030Date accessed: July 9, 2023 Google Scholar ]. The added advantage of vaccines is that they can reduce the need for antibiotic prescribing, through a reduction of the disease itself (bacterial vaccines) or a reduced number of bacterial superinfections (viral vaccines). Because antibiotic use is a key driver of AMR, a lower need for antibiotic prescribing can have knock-on benefits, slowing development, and spread of resistance in the population. In addition, evolution of vaccine resistance is less likely than AMR development, because vaccines have a multiplicity of targets and are mostly used prophylactically against invasive infection [ [4] Kennedy D.A. Read A.F. Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance. Proc Natl Acad Sci USA. 2018; 18: 12878-12886https://doi.org/10.1073/pnas.1717159115 Crossref Scopus (56) Google Scholar ]. Serotype replacement, such as after the implementation of Streptococcus pneumoniae vaccination, might reduce vaccine sustainability [ [5] Løchen A. Croucher N.J. Anderson R.M. Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency. Sci Rep. 2020; 1018977https://doi.org/10.1038/s41598-020-75691-5 Crossref PubMed Scopus (58) Google Scholar ]. However, this is a much slower process, and vaccine serotype coverage can be updated over time. For mAbs, antigenic escape could occur, but this can be overcome by using mAbs cocktails or bi-specific mAbs. Moreover, mAbs tend to have a long half-life, extending their clinical efficacy [ [6] Esposito S. Amirthalingam G. Bassetti M. Blasi F. De Rosa F.G. Halasa N.B. et al. Monoclonal antibodies for prophylaxis and therapy of respiratory syncytial virus, SARS-CoV-2, human immunodeficiency virus, rabies and bacterial infections: an update from the World Association of Infectious Diseases and Immunological Disorders and the Italian Society of Antinfective Therapy. Front Immunol. 2023; 141162342https://doi.org/10.3389/fimmu.2023.1162342 Crossref Scopus (2) Google Scholar ].